Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose ]

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to Day 49 ]

Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline [ Time Frame: Baseline ]

Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24 [ Time Frame: Day 24 ]

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1 [ Time Frame: Day 1 ]

Anti-PF-05231023 antibodies and neutralizing antibodies were analyzed only for participants who received PF-05231023 as per planned analysis. One sample at Day 1 was inadvertently tested for neutralizing antibody even though the corresponding anti-PF-05231023 antibody was negative.

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39 [ Time Frame: Day 39 ]

Anti-PF-05231023 antibodies and neutralizing antibodies were analyzed only for participants who received PF-05231023 as per planned analysis. One sample at Day 39 was inadvertently tested for neutralizing antibody even though the corresponding anti-PF-05231023 antibody was negative.

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49 [ Time Frame: Day 49 ]

Original Primary Outcome Measures ICMJE (submitted: August 22, 2012)

Evaluate the safety and tolerability of multiple intravenous doses of PF-05231023 administered once weekly to obese adult subjects with hypertriglyceridemia with and without Type 2 diabetes mellitus (T2DM). [ Time Frame: 27 Days ]

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose [ Time Frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hours (pre-dose) on Day 8 ]

AUCtau was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose [ Time Frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hour (pre-dose) on Day 8 ]

Tmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Cmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose [ Time Frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29 ]

AUCtau was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Tmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Cmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023 [ Time Frame: 0 (pre-dose), 0.5 (end of infusion ), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1; Day 4, 0 hour (pre-dose) on Day 8; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24, 25, 29 ]

Rac was obtained from AUCtau after last dose (Day 22) divided by AUCtau after single dose (Day 1). Rac was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Rac was obtained from AUCtau after last dose (Day 22) divided by AUCtau after single dose (Day 1). Rac was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Cmin was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose [ Time Frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49 ]

Cav was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-Life was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Characterize the pharmacokinetics of PF-05231023 after multiple intravenous doses administered once weekly to obese adult subjects with hypertriglyceridemia with and without Type 2 diabetes mellitus (T2DM). [ Time Frame: 27 Days ]

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus

Official Title ICMJE

A Phase 1, Placebo-controlled, Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Iv Doses Of Pf-05231023 In Obese Hyperlipidemic Adult Subjects With And Without Type 2 Diabetes Mellitus On A Background Of Atorvastatin

Brief Summary

This is a trial in obese subjects who have poor lipid control with and without Type 2 diabetes mellitus to study the safety, tolerability and pharmacokinetics of multiple doses of PF-05231023

0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks

Drug: 25 mg PF-05231023

25 mg IV once a week for 4 weeks

Drug: 50 mg PF-05231023

50 mg IV once a week for 4 weeks

Drug: 100 mg PF-05231023

100 mg IV once a week for 4 weeks

Drug: 150 mg PF-05231023

150 mg IV once a week for 4 weeks

Study Arms

Placebo Comparator: Placebo Arm

Intervention: Other: Placebo

Experimental: 25 mg

Intervention: Drug: 25 mg PF-05231023

Experimental: 50 mg

Intervention: Drug: 50 mg PF-05231023

Experimental: 100 mg

Intervention: Drug: 100 mg PF-05231023

Experimental: 150 mg

Intervention: Drug: 150 mg PF-05231023

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Enrollment ICMJE

107

Completion Date

September 2013

Primary Completion Date

August 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Male and female subjects of non-childbearing potential between the ages of 30 and 70 years with and without a diagnosis of Type 2 diabetes mellitus (according to the American Diabetes Association guidelines).